A study of the tubular secretory abnormality in renal tubular acidosis (RTA) is being carried out. Rats are injected with LiCl in order to produce a defect in H ion secretion and metabolic acidosis which resembles "distal" RTA in humans. By micropuncture techniques, intraluminal pH is being measured with glass microelectrodes in proximal and distal convoluted tubules, as well as total CO2 by the microcalorimetric method. The animals develop metabolic acidosis and excrete an inappropriately large amount of HCO3 in their urine, which has a high pH. Thus far, results show that pH in the proximal and distal tubules is the same as in normal rats.. However, fractional HCO3 reabsorption is decreased in the proximal tubules of the RTA rats, and a larger than normal fraction reaches the end of the distal tubules. Collectiong duct function, as judged by fractional HCO3 reabsorption between the end of the distal tubule and final urine seems to be normal. These results thus far support the view that "distal" RTA caused by LiCl is due to a leak of HCO3 from the proximal tubules into the final urine. Further studies will be carried out to test collecting duct function by infusing Na2SO4 i.v. The study of RTA will be extended to another model of "proximal" RTA, induced by maleate. Similar techniques of tubular fluid pH and CO2 measurements will be employed to determine the site and character of the defects.